The invention relates to antithrombogenic extracorporeal blood circuits and components thereof, such as hollow fiber membranes, blood tubing, and filters, and their use in hemofiltration, hemodialysis, hemodiafiltration, hemoconcentration, blood oxygenation, and related uses.
For a treatment of a patient suffering from renal failure, various blood purifying methods have been proposed in which blood is taken out from the living body of the patient to be purified and the purified blood is then returned into the body. For example, the blood purification methods utilizing extracorporeal circulation are classified into the following types: hemodialysis (HD) by diffusion, hemofiltration (HF) which performs body fluid removal/substitution by ultrafiltration, and hemodiafiltration (HDF) in which HD and HF are combined.
The above-mentioned methods are implemented using a hemodialyzer. The dialyzer is the piece of equipment that actually filters the blood of waste solutes and fluids (e.g., urea, potassium, creatinine, and uric acid). Almost all dialyzers in use today are of the hollow-fiber variety. A cylindrical bundle of hollow fibers, whose walls are composed of semi-permeable membrane, is anchored at each end into potting compound (a sort of glue). This assembly is then put into a clear plastic cylindrical shell with four openings. One opening or blood port at each end of the cylinder communicates with each end of the bundle of hollow fibers. This forms the “blood compartment” of the dialyzer. Two other ports are cut into the side of the cylinder. These communicate with the space around the hollow fibers, the “dialysate compartment.” Blood is pumped via the blood ports through this bundle of very thin capillary-like tubes, and the dialysate is pumped through the space surrounding the fibers. Pressure gradients are applied when necessary to move fluid from the blood to the dialysate compartment.
Hemodialysis is an important procedure that plays the role of an artificial kidney and replaces all vital functions due to chronic or acute kidney failure. The dialyzer may be used for the treatment of patients with renal failure, fluid overload, or toxemic conditions, and can be configured to perform HD, HF, HDF, or hemoconcentration.
While the blood is being transported to and from the body or cleaned in the dialyzer, an anticoagulant, such as heparin, may be added to prevent clotting or thrombosis. For patients receiving continuous renal replacement therapy (CRRT) (i.e., continuous dialysis 24 hours/7 days a week), heparin is typically given as a bolus systemically to prevent clogging of filter membranes during dialysis due to coagulation of blood. In cases where no heparin is administered filters clog 27% of the time, while with heparin filters clog 17% of the time (see Richardson et al., Kidney International 70:963-968 (2006)). For patients receiving intermittent hemodialysis (IHD) (intermittent dialysis of about 4 hours twice daily), typically no heparin is administered. During IHD the filters clog 20-30% of time (see Manns et al., Critical Care Medicine 31:449-455 (2003)). When the filters clog, the dialysis procedure is interrupted, and the filters are flushed with saline solution to clear the thrombus. In patients undergoing chronic hemodialysis (e.g., hemodialysis for extended hours at a time and with multiple sessions during a week) it is common to use heparin in bolus amounts to reduce the rate of filter clogging.
While advantageous, the use of heparin in some patients can be complicated by allergic reactions and bleeding, and can be contraindicated for use in patients taking certain medications.
Some medical procedures require the use of extracorporeal oxygenating methods, where blood is taken out from the living body of the patient to be oxygenated and the oxygenated blood is then returned to the body. For example, oxygenator devices implementing such extracorporeal oxygenating methods include heart-lung bypass units or extracorporeal membrane oxygenation (ECMO) machines used during open heart surgery, such as coronary artery bypass grafting (CABG) and cardiac valve replacement, or used to treat respiratory distress syndrome or respiratory insufficiencies. During open heart surgery, devices for hemoconcentration can also be used to increase various blood components within the patient, thus minimizing the risk of post-operative bleeding. These hemoconcentrators can be used in-line with an extracorporeal circuit that includes an oxygenator device, such as a heart-lung bypass unit.
Based on these treatments that require the use of pumping blood out of and into a patient, there is a need for extracorporeal blood circuits that have reduced thrombogenicity. In particular, there is a need for methods and compositions to provide a polymeric component of an extracorporeal blood circuit with a surface that minimizes the rate of thrombosis upon exposure to blood.